Applying the AIM Concept in Support of Developing Improved In Vitro–In Vivo Relationships for OIPs - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 379

Table 12.2 Descriptive statistics for the cumulative mass-weighted
APSDs for MDI-delivered salbutamol (100 µ g/actuation) based on ISM

( From [ 42 ] —used with permission )
Confi guration ACI-AIT inlet ACI-USP/Ph.Eur. inlet
MMAD (µm) 2.7 ± 0.0 3.0 ± 0.1
GSD 1.6 ± 0.0 2.1 ± 0.3
n = 5 replicates per apparatus/inlet confi guration; mean ± SD

ACI ( IM in Fig. 12.12b ), both indicated that replacing the USP/Ph.Eur. induction
port with the AIT resulted in a slight shift to fi ner sizes and decreased APSD
“spread,” based on comparisons of GSD . However, although the decrease in MMAD
determined was just below statistical signifi cance for MMAD , the corresponding
decrease in GSD was signifi cant (Table 12.2 ).
This behavior is comparable with that observed in a previous investigation by the
same group, using a Next Generation Pharmaceutical Impactor (NGI) with a similar
MDI-delivered formulation containing salbutamol and sampling at the slightly
higher fl ow rate of 30 L/min [ 45 ] (Fig. 12.13a ).
In that previous investigation [ 45 ], a similar movement of the aerosol APSD to
fi ner sizes was also seen evaluating a DPI (Fig. 12.13b ). Taken as a whole, these
measurements indicate that use of the AIT can be expected to result in impactor-
sized aerosols that have higher FPF values than those that would be obtained using
the USP/Ph.Eur induction port. Notwithstanding the fact that the upper bound size
for FPF 6.8 μm in the Newman-Chan correlation [ 2 ] shown in Fig. 12.5 is at a signifi -
cantly larger size than in these validation studies, such a trend, if maintained at the
larger upper size limit for FPF , would be in keeping with a movement of the values
nearer the line of identity and therefore closer to the demonstration of IVIVCs, at
least with lung deposition data using gamma scintigraphy.
Grouped salbutamol mass deposition data (mean ± SD) from the study of Copley
et al. [ 42 ] are summarized in Table 12.3 , as these are the measures on which the
comparability of AIM versus full-resolution CI measurements are perhaps best
evaluated. Note that CPM >4.7 μm included the mass retained by the inlet as well as that
penetrating to stage 2 of the ACI or the upper impaction stage of the AIM-pHRT
system.
Values of coarse particle mass ( CPM >4.7 μm ), fi ne particle mass ( FPM <4.7 μm ), and
extra-fi ne particle mass ( EPM <1.1 μm ) all determined ex MDI valve, were calculated
from the individual component deposition data, and are summarized in Table 12.3 .
The change from the USP/Ph.Eur. induction port to an AIT with the full-resolution
impactor resulted in a signifi cant decrease in CPM >4.7 μm , to values that were consistent
with the same metric determined by the AIM-pHRT system with AIT. On the other
hand, values of FPM <4.7 μm and EPM <1.1 μm were insignifi cantly affected. These fi ndings
demonstrated the suitability of the abbreviated system with the AIT compared with its
full-resolution counterpart. Importantly, they also indicated that the change of induc-
tion port, as expected, had more infl uence on the ballistic fraction of the incoming
dose, rather than on the aerosol that penetrated beyond the inlet into the CI.